Smooth muscle glucose metabolism promotes monocyte recruitment and atherosclerosis in a mouse model of metabolic syndrome

Valerie Z. Wall, Shelley Barnhart, Jenny E. Kanter, Farah Kramer, Masami Shimizu-Albergine, Neeta Adhikari, Thomas N. Wight, Jennifer L. Hall, Karin E. Bornfeldt

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Metabolic syndrome contributes to cardiovascular disease partly through systemic risk factors. However, local processes in the artery wall are becoming increasingly recognized to exacerbate atherosclerosis both in mice and humans. We show that arterial smooth muscle cell (SMC) glucose metabolism markedly synergizes with metabolic syndrome in accelerating atherosclerosis progression, using a low-density lipoprotein receptor-deficient mouse model. SMCs in proximity to atherosclerotic lesions express increased levels of the glucose transporter GLUT1. Cytokines, such as TNF-α produced by lesioned arteries, promote GLUT1 expression in SMCs, which in turn increases expression of the chemokine CCL2 through increased glycolysis and the polyol pathway. Furthermore, overexpression of GLUT1 in SMCs, but not in myeloid cells, accelerates development of larger, more advanced lesions in a mouse model of metabolic syndrome, which also exhibits elevated levels of circulating Ly6Chi monocytes expressing the CCL2 receptor CCR2. Accordingly, monocyte tracing experiments demonstrate that targeted SMC GLUT1 overexpression promotes Ly6Chi monocyte recruitment to lesions. Strikingly, SMC-targeted GLUT1 overexpression fails to accelerate atherosclerosis in mice that do not exhibit the metabolic syndrome phenotype or monocytosis. These results reveal a potentially novel mechanism whereby arterial smooth muscle glucose metabolism synergizes with metabolic syndrome to accelerate monocyte recruitment and atherosclerosis progression.

Original languageEnglish (US)
JournalJCI Insight
Volume3
Issue number11
DOIs
StatePublished - Jun 7 2018

Bibliographical note

Copyright:
This record is sourced from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Keywords

  • Atherosclerosis
  • Glucose metabolism
  • Vascular Biology

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